Q1 2024 Cardiff Oncology Inc Earnings Call

Participants

Kiki Patel; IR; Gilmartin Group

Mark Erlander; Chief Executive Officer, Director; Cardiff Oncology Inc

James Levine; Chief Financial Officer; Cardiff Oncology Inc

Marc Frahm; Analyst; TD Cowen

Joe Catanzaro; Analyst; Piper Sandler Companies

Andy Hsieh; Analyst; William Blair & Company

Presentation

Operator

Welcome to the Cardiff Oncology first-quarter 2024 financial results and business update conference call. (Operator Instructions) Please be advised that today's conference is being recorded.
I would now like to turn the conference over to Kiki Patel of Gilmartin Group. Please go ahead.

Kiki Patel

Thank you, operator. Joining us on the call today from Cardiff Oncology are Chief Executive Officer, Mark Erlander; and Chief Financial Officer, Jamie Levine.
During this conference call, management will make forward-looking statements, including, without limitation, statements related to guidance, results, and the timing of data readouts for onvansertib clinical trial. These forward-looking statements are based on the company's current expectations and inherently involve significant risks and uncertainties.
Our actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties. Factors that could cause results to be different from these statements include factors the company describes in the section entitled Risk Factors in our annual report on Form 10-K filed with the SEC for the year ended December 31, 2023.
Cardiff Oncology undertakes no duty or obligation to update any forward-looking statements as a result of new information, future events, or changes in its expectations.
With that, I turn the call over to Chief Executive Officer, Mark Erlander. Mark?

Mark Erlander

Well, thank you, Kiki. Good afternoon, everyone, and thank you for joining our conference call for the first quarter of 2024 business update.
It was less than a year ago that we announced that our clinical development platform, onvansertib, will focus on the first-line treatment of RAS-mutated metastatic colorectal cancer, or mCRC. The data we shared last August supported this move, and our focus on first line mCRC addresses a large patient population, almost 50,000 new patients a year in the United States for whom there have been no therapies approved in 20 years.
In the first quarter of 2024, three datasets added to the body of evidence supporting our first-line focus strategy. First was the ONSEMBLE data, which served as an independent and randomized dataset that replicated the efficacy signal in bev-naive patients observed in our Phase 1b/2 trial.
Second was our five posters presented at the annual meeting of the American Association for Cancer Research, or AACR. And finally was the publication of data in the peer-reviewed journal Clinical Cancer Research from the Phase 1b portion of our Phase 1b/2 KRAS-mutated mCRC trial.
I want to emphasize our conclusion that the collected data released in Q1 strongly supports our finding that adding onvansertib in standard of care, FOLFIRI and bevacizumab, which I will refer to as bev, has significant efficacy in RAS-mutated mCRC patients that are bev naive, that is patients that have had no prior treatment of bev.
Now during today's call, we have three topics to cover. First, I will provide a summary of the promising data we presented last month at AACR. Next, we will discuss our lead program in mCRC and provide updates around our ongoing CRDF-004 plan. And finally, we'll talk about our financial position that we disclosed today in our Form 10-Q.
So let's begin. Last month, the American Association for Cancer Research held its 2024 Annual Meeting in San Diego, in which Cardiff Oncology presented a total of five posters, all of which are available on our website. One poster described the design of our ongoing part of CRDF-004 trial.
A second poster presented data that supports our first-line strategy in mCRC by providing new translational data from our Phase 1b/2 trial in second-line KRAS-mutated mCRC. Three additional posters shared promising pre-clinical data in other cancer indications, including RAS wild-type mCRC, small cell lung cancer, and ovarian cancer, demonstrating the broad opportunity we see for onvansertib.
I would like to highlight some of the important data we presented in the poster on our lead program in RAS-mutated mCRC. In this poster, we presented both clinical data from the Phase 1b/2 trial and subsequent data from pre-clinical studies that forms the basis of the scientific rationale for our clinical plan. We also have demonstrated that bev naive patients within this trial had a higher objective response rate and a longer progression-free survival.
The additional pre-clinical data -- clinical data disclosed at AACR provide further evidence that onvansertib and bev have their pharmacological effect at two different nodes of the hypoxia pathway. We hypothesize that onvansertib and bev work in a synergistic manner, giving a one-two punch to the tumor. Our hypothesis was further strengthened by our pre-clinical, in vivo data and three KRAS-mutant mCRC xenograft model.
Combination treatment with onvansertib plus bev resulted in significant superior anti-tumor activity compared to monotherapy with either agent. And importantly, the combination treatment also resulted in a greater decrease in tumor vascularization compared to either agent alone. This filing provides rationale for further exploration of the combination of onvansertib and bev in additional indications or bev if FDA approved.
Collectively, the clinical and pre-clinical data presented at AACR in RAS mutated, second-line mCRC provides further validation of our ongoing CRDF-004 trial. We believe onvansertib will have a significant impact in the first-line setting, given that all patients are bev naive.
Now let's move on to our additional posters presented at AACR in therapeutic areas outside of our core focus of RAS-mutated mCRC. Today, most of the data we have generated in mCRC has been in RAS-mutated patients. And we are often asked if our therapy could work for patients who do not have a RAS mutation.
At AACR, we shared encouraging pre-clinical data in RAS wild-type mCRC, meaning these models were derived from patients who did not have a RAS mutation. Our pre-clinical study in RAS wild-type mCRC. patient-derived xenograft, or PDX, model and to assess the efficacy of onvansertib as monotherapy and in combination with the EGFR inhibitor, cetuximab, which is the standard of care for RAS wild-type mCRC patients. We evaluated models that were both sensitive to cetuximab and resistant to cetuximab.
In summary, onvansertib displayed robust anti-tumor activity as a single agent in cetuximab-sensitive and resistant PDX model. As for combination therapy, efficacy was enhanced when onvansertib and cetuximab were combined compared to monotherapy with either agent alone. In combination, onvansertib and cetuximab induce tumor stasis of regression in 90% or 18 of the 20 PDX models.
Overall, we are exceptionally pleased with our RAS wild-type pre-clinical data presented at AACR as it emphasizes that onvansertib has broad spectrum activity in mCRC, independent of RAS mutation status. This provides sound rationale for us to consider future clinical trials in RAS wild-type mCRC.
I now would like to share the data we presented at AACR, demonstrating onvansertib anti-tumor activity across multiple tumor types outside of mCRC. If you recall, last September, we shared clinical data from our investigator-initiated trial in extensive-stage small cell lung cancer for onvansertib as a single agent, demonstrating a confirmed partial response with 50% shrinkage of patient's tumor among the first seven patients treated on the trial.
While we were impressed by onvansertib's single-agent activity, we believe a combination strategy would be the optimal approach to treating this aggressive disease. At that time, we disclosed that our clinical path forward in small cell lung cancer will be the combination strategy of onvansertib and paclitaxel, which is one of the standards of care for second-line small cell lung.
At AACR, we presented pre-clinical evidence that supports this clinical plan. In vitro, the combination of onvansertib plus paclitaxel synergistically inhibited tumor proliferation and cell lines for small cell lung cancer. In vivo, the combination was well tolerated and highly effective in cisplatin-sensitive and resistant PDX models for small cell lung cancer. These findings support the scientific rationale for a planned investigator-initiated trial combining onvansertib with paclitaxel as a promising treatment strategy for extensive-stage small cell lung cancer patients.
Our final poster presented at AACR evaluated the combination of onvansertib plus carboplatin or gemcitabine in high-grade serous ovarian cancer, where both of these agents are standard of care. In vitro, onvansertib is synergistic in combination with carboplatin as well as with gemcitabine in an ovarian cell line. In vivo, both combinations demonstrated anti-tumor activity in platinum-resistant ovarian cancer PDX models and was well tolerated.
Overall, we believe that these data support the potential of onvansertib to improve standard of care treatment for platinum-resistant ovarian cancer patients. At the moment, we are still determining our path forward in this indication.
So in summary, the data we presented at AACR this year provided strong scientific rationale for the clinical development of onvansertib across multiple tumor types and various combinations. And our RAS-mutated mCRC data provided further validation of our lead program and our ongoing CRDF-004 clinical trial.
Now, turning to our second agenda item, CRDF-004. These are ongoing Phase 2 trials evaluating first line patients with RAS-mutated mCRC. Onvansertib is being added to standard care -- current standard of care, which is either full FOLFIRI plus bev or FOLOFOX plus bev.
We plan to enroll a total of 90 patients who will be randomized to receive either 20 mig of onvansertib for standard of care, 30 migs of onvansertib pus standard of care, or standard of care alone. We are working closely with our partner, Pfizer Ignite, who is conducting the clinical execution of the trial. And we are highly confident in Pfizer's ability to operationally execute, given their track record of success.
Currently, we have 24 activated clinical trial sites. In August of 2023, when we decided to move forward with the CRDF-004 trial, we forecasted that we would be able to share additional data from the trial in the Q2, Q3 2024 timeframe. As of today and based on the actual enrollment trends at our activated site for the past few months, our expectation for the timing of an initial readout is now in the second half of this year or Q3, Q4.
I want to make it clear that this timing for the readout is solely based on the pace of enrollment. We, together with Pfizer Ignite, feel confident in our ongoing site activation and enrollment efforts. And we believe that we have all the resources to meet this timing. We anticipate this additional top-line data release will include objective response rate for approximately half of the 90 patients we expect to enroll in the trial.
Now, I would like to turn the call over to Jamie to discuss our third agenda item, our first-quarter 2024 financial update.

James Levine

Thank you, Mark. Earlier today, we issued a press release summarizing our financial results for the first quarter ending March 31, 2024. You can also find additional information in our Form 10-Q for the first quarter filed with the SEC earlier today.
Turning to our balance sheet. Cash and short-term investments as of March 31, 2024, totaled $67.2 million, and our cash used in operating activities was $7.7 million in Q1 2024. We believe that our current cash resources provide us with cash runway into the third quarter of 2025, which is well beyond the updated timing for the initial readout from the CRDF-004 Mark just discussed.
With that, I'll turn the call back over to Mark.

Mark Erlander

Thank you, Jamie. Let me close the call by emphasizing our conviction in our clinical development strategy to add onvansertib to the standard of care in first-line RAS-mutated mCRC. We followed the data that was available at the time. And with the ONSEMBLE clinical data and the AACR data announced this quarter, our confidence continues to grow.
And that brings us to where we are today. Our ongoing CRDF-004 trial for the treatment of first-line RAS-mutated mCRC. Overall, we believe that the initial data readout of CRDF-004 has the potential to be an important value inflection point for Cardiff Oncology and for the nearly 50,000 patients diagnosed with RAS-mutated mCRC each year. We look forward to sharing an update on the trial later this year.
With that, I will now open the call up for questions. Operator?

Question and Answer Session

Operator

Thank you so much. (Operator Instructions) Marc Frahm, TD Cowen.

Marc Frahm

Thanks for taking my questions. If we just start off on the (inaudible) guidance on the -- on when the interim data might become available. Can you just clarify how much of the small push-out was really the enrollment pace once sites are open versus maybe just some delays getting the sites up and running as quickly as you'd hoped?

Mark Erlander

Well, yeah. Let me just -- thanks, Mark, for the question. And let me just step back for a minute and just talk about the CRDF-004 trial Over the last month or so, Dr. Fairooz Kabbinavar, our Chief Medical Officer, and I have been going across the country and visiting with the principal investigators of -- that are participating in our trial.
And Fairooz has actually been taking them through the previous data in the Phase 1b/2 and the ONSEMBLE data. And what I would say, universally, is that there is a high amount of enthusiasm with all of the principal investigators we have met.
And the reason for that is not only because of the actual data that they're seeing a building up to the trial that they are participating in now, but also that the onvansertib does provide a novel, new option for first-line -- in the first-line setting, where, as you know, there have been no new therapies for 20 years. Also, one of the key things that makes them enthusiastic is the actual design of the trial because we are adding on bev. And so we're building it on to current standard of care and not replacing standard of care.
And finally, also, there are no competing trials for first-line RAS-mutated mCRC. So as you know, as I was saying earlier in the call, when we started -- when we made the decision this summer of '23 to basically start CRDF-004, that's when we then announced in August of '23, prior to the trial start, the forecast to share data in the Q2, Q3 timeframe of 2024.
Now that we've got several months of the enrollment in the patient enrollment, we are able to now make a more accurate projection of the data share. And that is more into Q3, Q4.
And I think one thing, last thing I'd say, Mark, is that -- why are we so confident of this timing? That's really because we are leveraging Pfizer's resources, Pfizer Ignite's resources; their techniques; and their capabilities in multiple areas around the execution of this trial. And we are very confident of their ability to execute.

James Levine

Great. That helpful. And then maybe just as we get to that data, could you read some of the scenario planning that you and the team are going through in terms of the data? I know it's not a formal statistical analysis there. But is there a scenario where it could get shut down, either more from a utility perspective or also, on the other end of the spectrum, make you want to accelerate plans to open up 005 even faster and not have to wait for all 90 patients?

Mark Erlander

I mean, I think right now, of course, what we're saying is that we will be looking to share data, initial data, in the Q3, Q4 timeframe. And we should have approximately half the patients of the trial, approximately that, with at least one post-baseline scan.
I mean, one thing I would say about that timing is that -- it's a great question, Mark -- is that 004, from the FDA's point of view, is really a dose confirmation trial of (inaudible) and so the faster we can get to the FDA with a dose, of course, the better off we are and better off we are as far as our timeline before going our registrational trial.

James Levine

Okay, thanks.

Operator

Thank you. Joe Catanzaro, Piper Sandler.

Joe Catanzaro

Hey, everybody. Thanks for taking my questions here. Maybe first one with the slight push in the initial readout from 004. I'm wondering if there's a possibility of maybe seeing another cut of the ONSEMBLE cohort before then just getting a longer follow-up, a better sense of the durability of responses, and how that's shaking out between the arms of the trial the bev naive has experienced. So any thoughts there would be helpful.

Mark Erlander

Yeah, thanks, Joe, for the question. I mean, as we sit here today, we did announce the data on February 29 for the ONSEMBLE trial. And we felt that that was a very robust dataset have propelled us with even greater confidence into our 004. As we sit here now, we don't have plans to have a continued follow-up of the ONSEMBLE data, no.

Joe Catanzaro

Okay. Thanks. And then maybe my follow-up is on the pre-clinical work at AACR on the RAS wild-type mCRC scenario. I recall years back the synthetic lethality idea of PLK-1 inhibition in the context of a mutant RAS. It seems like you're thinking outside of that, and you mentioned potentially exploring it. Maybe you could just elaborate whether there's opportunity to explore that clinically and think about that population of patients within the context of a potential future pivotal front-line trial.

Mark Erlander

Yeah. Great question, Joe. I think, first of all, when you look at RAS wild-type and RAS-mutant tumors, colorectal, those are very different. It's very different animals in the sense that the biology. And so as you know, we have shown synthetic lethality in RAS0mutant background.
In RAS wild type, I think it's a different biology. And I think that we are seeing very interesting finding where we are combining with cetuximab. And so I think as we sit here today, we are evaluating what kind of trial design that would be in the wild-type setting. But we haven't -- no, we have not made any move yet in that area. Our focus, as you see here today, continues to be 004 and getting the data toward the registrational trial.

Joe Catanzaro

Okay, got it. That's all helpful. Thanks for taking my questions.

Mark Erlander

No, absolutely. Thanks, Joe.

Operator

Thank you. Andy Hsieh, William Blair.

Andy Hsieh

Great. Thanks for taking our questions. A couple of quick ones from us, if you don't mind. So in terms of clinical sites, I believe, Mark, you said 24 sites right now. I believe it was 20 before. And is your end goal being 30, total, by the end of the enrollment completion?

Mark Erlander

Yeah. Thanks, Andy, for that question. So you're right. As of today, we have 24. And our goal actually in working with Pfizer Ignite is to activate 35 sites. And we are also looking at some additional sites.
But one of the things to keep in mind is this is just a very dynamic process in a sense that we continue to evaluate sites. And if the site is not performing, then that site could be replaced with another site. So the number is not always static. It's really more dynamic as we go through this trial continuing to activate sites.

Andy Hsieh

Okay, that's helpful. Thank you. And just kind of a follow-up on Mark's question before. You mentioned about Project Optimus, two doses in a 004 study. Is it conceivable to bring two doses in the pivotal study? Is that a potential scenario? And I guess, from a FDA perspective beyond confirmation of safety, efficacy, what else are they looking at before giving you the okay to start a pivotal study?

Mark Erlander

Right. Thanks for the question. Just to answer those questions literally, first off, we don't expect to go in to the registrational trial with two doses. We plan to have a single dose. And you're right, what the FDA looks for is really -- is there a difference between the efficacy between the two doses and is there a difference in the safety?
Both those things, we will be continuing to evaluate not only using our existing data, but also the -- obviously, the 004 data. And like I said to Mark, our goal -- our gate to the registrational trial is this confirmation of dose with the FDA. So of course, we are very focused on getting that as soon as possible.

Andy Hsieh

Great. And maybe my last question has to do with the catalyst events. So Jamie, you talked about Q3 2025 being the cash runway. Perhaps, can you give us maybe a big-picture view? Obviously 004 study happening in the second half of this year. Any other potential data readouts that you can expect in the first three quarters of 2025 that could allow us to better appreciate the clinical activity of onvansertib?

James Levine

That's a great question. We are not prepared at this point to set dates on some of the investigator-initiated trials that we do actually have ongoing right now. Those could be, potentially, but we're just not prepared to (inaudible) put out in the public. Okay, this is the time that we would announce data on those trials. But clearly, we are looking at those as well, as we will continue to keep a laser focus on the 004 trial.

Andy Hsieh

Got it, I understand. All right. Thanks so much for answering all of our questions.

Mark Erlander

Thank you, Andy.

Operator

Thank you. And I will conclude the Q&A session as I see no further questions and hand them back to Mark Erlander. Thank you.

Mark Erlander

Thank you, operator. And this concludes our conference call. Thank you once again, everyone, for joining us this afternoon. Have a good day.

Operator

Thank you. You may all disconnect.